It has been established that speed is crucial for the management of acute ischemic stroke (AIS).1 Although traditional guidelines mainly provide treatment advice based on the standard time window, “tissue clock” illustrated by advance imaging has been shown to extend the treatment window for reperfusion therapies.2-4 At the 24th Hong Kong Medical Forum (HKMF), Dr. Mona Tse from the University of Hong Kong presented updates on AIS management with the latest clinical trial findings.
Recommendations for treatment of acute ischemic stroke (AIS) include reperfusion therapies, which are recombinant tissue plasminogen activator (TPA) intravenous (IV) thrombolysis and intraarterial (IA) mechanical thrombectomy. Rapid and complete implementation of these therapies is essential for neurological recovery. If treatment is delayed, the clinical outcomes deteriorate with time – 1.9 million neurons lost for every minute of delay.5
The American Heart Association (AHA) and the American Stroke Association (ASA) have updated the guidelines for the early management of AIS patients in 2018. The revised version stated that the extent and severity of early ischemic changes or acute hypoattenuation should not be regarded as a benchmark for physicians to withhold otherwise qualified patients for receiving IV alteplase.1 The guidelines also lifted restriction on the administration of IV alteplase in the older patients (>80 year of age), demonstrating that it is safe and effective to utilize IV TPA in older patients even when the time window (from symptom onset) reaches 3- to 4.5-h.1
The practice of TPA administration following idarucizumab was excluded in the 2018 AHA/ASA guidelines.1 Dr. Tse presented the data from a retrospective study in Germany, illustrating that there was no bleeding complications and no thrombotic events after receiving TPA following idarucizumab within 24-h. She believes the guidelines should be updated in the future to accept such practice because of its safety profile, in which IV TPA could benefit more patients who have taken idarucizumab within 24-h.
Dr. Tse noted that there could be differences in MRI brain images of patients suffering from the same middle cerebral artery (MCA) occlusion at the same time point since onset. She explained that patients with the same degree of occlusion would differ in collateral supply. She further elaborated that if a patient has a better collateral supply, the infarct core would grow slowly and generally be smaller in size, and that indicates a slower progressor and a potential candidate for reperfusion therapies.
It has been found that patients with unknown time of acute stroke onset benefit from IV alteplase. Since previous studies have demonstrated that symptom onset within 4.5-h can be predicted by a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR), Thomalla et al. studied 503 non-IA candidates with positive DWI-FLAIR mismatch who woke up experiencing the stroke symptoms or their last known well time was over 4.5-h.2 The group reported that IV alteplase administration guided by the mismatch could achieve better clinical outcome than placebo (90-day mRS 0-1; 53.3% vs. 41.8%; p=0.02).2
A similar benefit of advance imaging for treating AIS was also discovered in mechanical thrombectomy. Among AIS patients with last known well time ranging from 6- to 24-h earlier, compared to receiving standard care alone, the percentage of patients treated with thrombectomy and standard care achieving functional independence 90 days later were higher (90-day mRS 0-2; 49% vs. 13%).3 A concurring result was yielded in a study comparing the endovascular therapy plus medical therapy and medical therapy alone in ALS patients who were last known to be well from 6- to 16-h (90-day mRS 0-2; 45% vs. 17%; p<0.001).4
Both endovascular therapy studies have employed RAPID software for CT and MRI image analysis. Dr. Tse introduced RAPID, the software to the audience, citing its efficiency for generating infarct volume and calculating mismatch volume and ratio in 2 minutes, which would facilitate the patient selection. She believes this software should hopefully be included in Hong Kong Hospital Authority public hospitals soon.
“The late arriving patient with a small infarct core can have extremely robust treatment effects, so we can use a tissue clock to extend the treatment window to 9 hours for IV therapy and 24 hours for IA therapy,” said Dr. Tse. Since a considerable percentage of patients have very slow growth of ischemic cores for up to 24-h, it is anticipated that advance imaging guidance to identify mismatch between DWI-FLAIR could allow more patients to be treated with reperfusion therapies beyond the therapeutic prime window.6
1. Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e110.
2. Thomalla G, Simonsen CZ, Boutitie F, et al. MRI-guided thrombolysis for stroke with unknown time of onset. N Engl J Med. 2018;379(7):611-22.
3. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med. 2018;378(1):11-21.
4. Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378(8):708-18.
5. Saver JL. Time is brain – quantified. Stroke. 2006;37(1):263-6.
6. Akbers GW. Late window paradox. Stroke. 2018;49(3):768-71.